Ixodes scapularis ticks overwinter in the Northeast and Upper Midwest parts of United States, and transmit various human pathogens that include human anaplasmosis agent Anaplasma phagocytophilum. My preliminary data show that the presence of A. phagocytophilum in ticks increases the ability of I. scapularis to survive in the cold. I have identified an I. scapularis antifreeze glycoprotein, designated as IAFGP and demonstrate, via RNAi knockdown studies, the importance of IAFGP for the survival of ticks in a freezing environment. Transfection studies also show that IAFGP increases the viability of yeast cells subjected to low temperatures. Remarkably, I have found that A. phagocytophilum induce the expression of iafgp and thereby increase the cold tolerance of I. scapularis. These data define a molecular basis for symbiosis between A. phagocytophilum and I. scapularis. The mechanism by which A. phagocytophilum, induce iafgp expression is not understood. Therefore studies will be performed to elucidate the mechanism by which A. phagocytophilum influence vector gene expression for its own benefit as well as its vector host survival during freezing temperatures. Following are the specific aims that will be addressed to understand the mechanism: In aim 1, I will identify and characterize iafgp promoter in I. scapularis. The studies in this aim will address whether iafgp promoter is activated upon A. phagocytophilum infection. In aim 2, studies will be undertaken to characterize the role of host transcriptional activators that may be involved in iafgp promoter induction. Collectively, the proposed studies not only elucidate the molecular mechanisms of symbiotic association between A. phagocytophilum and I. scapularis ticks but also delineate a new approach to study host-pathogen interaction.